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Bioorganic and Medicinal Chemistry Letters
Volumn 22, Issue 8, 2012, Pages 2803-2806
Discovery of S-777469: An orally available CB2 agonist as an antipruritic agent
Author keywords

Antipruritics; Cannabinoid; CB receptor agonist; GPCR
Indexed keywords

ANTIPRURITIC AGENT; CANNABINOID 2 RECEPTOR AGONIST; S 777469; UNCLASSIFIED DRUG;
EID: 84859440706     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.02.072     Document Type: Article
Times cited : (47)
References (15)
  • 11
    • 84859444183 scopus 로고    scopus 로고
    • Estimation of in vivo psychoactivity: In order to qualitatively estimate the level of CB1 induced CNS side effects, test compounds were dissolved in MDAA and PEG solution and intravenously injected into the tail of the ICR mice (0.1 mg/kg and 1.0 mg/kg, n = 3 each). The apparent behavior of each mouse was observed at 15 min after injection and the score (5: Tonic convulsion; 4: Catalepsy; 3: Prone position, Sedation; 2: Crawling; 1: Decrease in locomotor activity; 0: Normal) was determined. The higher the score, the more potent are the CNS side effects
    • Estimation of in vivo psychoactivity: In order to qualitatively estimate the level of CB1 induced CNS side effects, test compounds were dissolved in MDAA and PEG solution and intravenously injected into the tail of the ICR mice (0.1 mg/kg and 1.0 mg/kg, n = 3 each). The apparent behavior of each mouse was observed at 15 min after injection and the score (5: Tonic convulsion; 4: Catalepsy; 3: Prone position, Sedation; 2: Crawling; 1: Decrease in locomotor activity; 0: Normal) was determined. The higher the score, the more potent are the CNS side effects.
  • 13
    • 84859440519 scopus 로고    scopus 로고
    • 3H]-CP55940 for each membrane fraction were determined by Scatchard plot analysis
    • 3H]-CP55940 for each membrane fraction were determined by Scatchard plot analysis.
  • 14
    • 84859446152 scopus 로고    scopus 로고
    • Cyclic AMP assay method: The CHO cells expressing hCB1 or hCB2 were seeded into 24-well plates. The cells were incubated at 37 °C for 20 min with compounds in the cAMP assay buffer (Hanks' solution with 20 mM HEPES, 0.1 mM IBMX, 0.2 mM Ro20-1724, 0.1% BSA). The cells were stimulated with 4 μM forskolin at 37 °C for 25 min (hCB1 cells) or 45 min (hCB2 cells). The cAMP concentrations in the cells were measured using cAMP kits (CIS Bio International)
    • Cyclic AMP assay method: The CHO cells expressing hCB1 or hCB2 were seeded into 24-well plates. The cells were incubated at 37 °C for 20 min with compounds in the cAMP assay buffer (Hanks' solution with 20 mM HEPES, 0.1 mM IBMX, 0.2 mM Ro20-1724, 0.1% BSA). The cells were stimulated with 4 μM forskolin at 37 °C for 25 min (hCB1 cells) or 45 min (hCB2 cells). The cAMP concentrations in the cells were measured using cAMP kits (CIS Bio International).
  • 15
    • 84859444184 scopus 로고    scopus 로고
    • In vivo assay (pruritic model): Crj:CD-1 (ICR) (Japan Charles River Lab.) mice were used for the scratching test to investigate the antipruritic effect. Test compounds were dissolved in acetone (Sigma). Compound 48/80 as a pruritogen dissolved at 75 μg/ml in isotonic saline (Otsuka Pharma.). Test compounds were administered as forced oral dosages to mice. After 1 h, 40 μl of pruritogen was injected intradermally into the back of mice. Thereafter, their behavior was videotaped to count the scratching behavior for 30 min. The % inhibition value was calculated with the equation: % inhibition = (B-A) - (C-A)/(B-A/100); scratching of control (n = 29) as A, scratching of vehicle (n = 6) as B, scratching of test mice (n = 6) as C
    • In vivo assay (pruritic model): Crj:CD-1 (ICR) (Japan Charles River Lab.) mice were used for the scratching test to investigate the antipruritic effect. Test compounds were dissolved in acetone (Sigma). Compound 48/80 as a pruritogen dissolved at 75 μg/ml in isotonic saline (Otsuka Pharma.). Test compounds were administered as forced oral dosages to mice. After 1 h, 40 μl of pruritogen was injected intradermally into the back of mice. Thereafter, their behavior was videotaped to count the scratching behavior for 30 min. The % inhibition value was calculated with the equation: % inhibition = (B-A) - (C-A)/(B-A/100); scratching of control (n = 29) as A, scratching of vehicle (n = 6) as B, scratching of test mice (n = 6) as C.

* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.